The PI is a clinical psychologist in the Department of Psychiatry at Washington University School of Medicine, an international leader in psychiatric research with well-established research programs in addictions and genetics. The PI is developing a program of research on genetic and environmental contributions to alcohol use and dependence rooted in a developmental psychopathology framework. Her research focuses on problem drinking behaviors and associated psychiatric disorders from the adolescent to young adult years, with an emphasis on the progression through stages of use and the rate at which those transitions occur. The role of childhood assaultive trauma in shaping the course of alcohol use disorders has figured prominently in her work in this area and will be a major focus of the proposed K-award project, which integrates her extensive experience with trauma-exposed populations (clinical as well as research experience) with behavioral genetic approaches to studying substance-related behaviors. The K08 will be instrumental in moving her toward her goal of establishing an independent R01-funded research program aimed at characterizing the course of alcohol use and alcohol use disorders in genetically-informative frameworks. This program of research will address three core issues: 1) the degree of variability in heritable and environmental influences on alcohol- related outcomes across stages of use and as contributors to the rate of transitions through these stages;2) the extent to which the contributions of use and misuse of other substances, trauma exposure, and co-occurring psychiatric disorders to alcohol-related problems vary over time;and 3) the nature of the association between short-term patterns of drinking behaviors and current as well as future alcohol-related problems, including the consistency of this relationship across developmental periods. A second critical component of the PI's long-term career plans is to increase collaborations with researchers conducting treatment outcome studies and prevention program development to promote translational efforts of this line of research. The proposed career development plan, which will be undertaken under the guidance of mentor Dr. Andrew Heath, co-mentor Dr. Kenneth Sher, and consultants Dr. James Anthony and Dr. Phillip Wood, is designed to prepare the PI for the transition to independent investigator status through tutorials, hands-on experience conducting statistical analyses with existing data as well as data from the proposed new data collection, and formal coursework. The four major goals of the training plan are to gain expertise in genetically-informative approaches to characterizing the course of alcohol use, advance skills in longitudinal data analysis, establish a foundation in the basic principles of genetics and genomics, and develop proficiency in web-based data collection on alcohol-related behaviors. The proposed research project will address genetic and environmental contributions to two dimensions of the course of alcohol use: the rate of progression between drinking milestones, and day to day patterns in alcohol use. Their underrepresentation in alcohol-related studies makes identifying distinct vulnerabilities or patterns of use in women a challenging task. The current project focuses exclusively on female samples in an effort to address this issue. Progression through drinking milestones, specifically, the potential mediating and moderating effects of psychiatric and psychosocial risk factors (e.g., conduct disorder, depression, childhood assaultive trauma) on genetic contributions to transitions in alcohol use and dependence, will be examined in secondary analyses with retrospective reports of drinking history in two existing datasets. The first is a sample comprised of 4,417 female twins from the Missouri Adolescent Female Twin Study (MOAFTS) and 535 female participants from the Missouri Family Study, a high risk alcoholism family study oversampled for African-American ethnicity (50%);and b) 2,632 female twins from an Australian twin cohort. Day to day patterns of alcohol use will be investigated in a new web-based data collection with a subset of twin pairs (n=100), selected by childhood sexual abuse (CSA) status from MOAFTS. Brief telephone diagnostic interviews will be followed up with weekly web-based surveys of alcohol consumption and other substance use (as well as exposure to substance-using environments) administered in a daily diary format over a period of 12 weeks. An additional measure assessing trauma exposure in the previous 12 weeks will be included in the week 12 assessment. One year after completion of the web-based component of the study, participants will be re-contacted for a follow-up telephone interview covering the same domains of psychiatric and psychosocial functioning covered in the baseline interview. The 12 month follow-up will also involve recall of substance use and related behaviors reported over the 12 week assessment period in an effort to test consistency in reporting between prospective reports and retrospective summaries. Analyses will be aimed at quantifying familial liability and environmental contributions to patterns of problem alcohol use and determining whether women with CSA histories exhibit unique patterns of use. The project will provide feasibility data for an R01 application to conduct a longitudinal genetic association study of short-term patterns of alcohol and other substance use in adolescents using web-based data collection methods. By enhancing understanding of genetic and environmental contributions to the course of alcohol use and the development of problem drinking behaviors in women, the proposed K-award project will facilitate development of interventions targeting high-risk patterns of use and transition points in drinking course distinguished by elevated liability to problem alcohol use. PUBLIC HEALTH RELEVANCE: This K08 award will provide the applicant with the training and resources to establish a program of research that will inform etiological models of alcohol use disorders and prevention efforts by studying the course of alcohol use within genetically-informative frameworks. The proposed project's goal of quantifying genetic and environmental contributions to patterns of problem drinking and their variation across stages of alcohol use in women will help identify those junctures where drinking course can be most easily modified.